{"doi":"10.1111/php.70049","title":"Nanoengineered photosensitizers for photodynamic priming to overcome P‐glycoprotein‐mediated multidrug resistance","abstract":"P-glycoprotein (P-gp, ABCB1)-mediated multidrug resistance (MDR) remains a significant barrier to successful chemotherapy outcomes for cancer patients. While photoactivation of verteporfin (VP), a photosensitizer, has demonstrated success for overcoming MDR through direct protein aggregation upon photoactivation and through adenosine triphosphate (ATP) depletion, the impact of VP's formulation on P-gp function and cellular energetics has not been fully characterized in this context. In this study, we screened four well-established VP formulations-liposomal VP (L-VP), lysophosphatidylcholine-conjugated VP (lysoPC VP), liposomal formulation of lysoPC VP (L-lysoPC VP), and a self-assembled VP nanoaggregate (NanoVP), with a free form of VP as a control-for their ability to inhibit P-gp. Using a combination of in vitro intracellular VP accumulation assays, P-gp substrate retention experiments, and Seahorse-based metabolic profiling, we identified NanoVP as the lead formulation for P-gp modulation in cancer cells. NanoVP effectively depleted ATP in drug-resistant cancer cells, while being recognized as a P-gp substrate. Photodynamic priming with NanoVP at sub-cytotoxic light doses enhanced P-gp substrate retention within the cells without damaging P-gp protein, indicating ATP depletion as the primary mode of functional inhibition. These findings highlighted NanoVP's clinical potential to enhance chemotherapeutic efficacy via photoactivation-based modulation of P-gp's function in multidrug-resistant cancers.","journal":"Photochemistry and Photobiology","year":2025,"id":537157,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1422496,"name":"Anju Meda","orcid":"0009-0002-5059-8939","position":1,"is_corresponding":false},{"id":1422497,"name":"Kaitlyn A. Moore","orcid":"0009-0003-1775-4685","position":2,"is_corresponding":false},{"id":1065451,"name":"Payal Srivastava","orcid":"0000-0003-3295-4442","position":3,"is_corresponding":false},{"id":1273667,"name":"Anika Dasgupta","orcid":null,"position":4,"is_corresponding":false},{"id":452640,"name":"Andaleeb Sajid","orcid":"0000-0001-6248-4985","position":5,"is_corresponding":false},{"id":334608,"name":"Suresh V. Ambudkar","orcid":"0000-0002-2639-4955","position":6,"is_corresponding":false},{"id":231442,"name":"Huang‐Chiao Huang","orcid":"0000-0002-5406-0733","position":7,"is_corresponding":false},{"id":1066069,"name":"Idrisa Rahman","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:52:09.056872Z","pmid":"41235707","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}